1. Field of the Invention
The invention relates generally to screening and diagnostic methods and more particularly to methods for detecting and diagnosing Mycobacterium tuberculosis. 
2. Description of the Related Art
Mycobacterium tuberculosis is the bacterial agent responsible for human pulmonary tuberculosis. Almost one third of the world's population suffer from this infectious disease. Over three million people die yearly from tuberculosis (TB), the largest single infectious cause of mortality worldwide. Of those infected with Mycobacterium tuberculosis, approximately 5% manifest the disease within a few years after infection. Upon initial infection, the mycobacteria enter unactivated macrophages and multiply. Following a rapid growth phase, infected macrophages are sequestered by newly recruited activated macrophages.
Mycobacterial dormancy results in a disease stage termed latent tuberculosis. An individual with latent tuberculosis may later develop a case of reactivated tuberculosis, and in fact, the majority of the tuberculosis cases reported in the United States are the result of reactivation of a latent mycobacterial infection and not an initial infection. Reactivation of the Mycobacterium tuberculosis bacilli usually occurs in the apex of the lung where large numbers of tubercle bacilli cause necrosis of the small bronchi of the lung. The characteristic bloodstained sputum of tuberculosis results from the erosion of small blood vessels during this necrotic process.
In many places, the tuberculin skin test is the only available diagnostic test for those infected with TB. The tuberculin skin test is only capable of identifying individuals either exposed to the pathogen or vaccinated against the pathogen. Due to the high number of latently infected individuals and the risk of reactivation of tuberculosis in those individuals, diagnostics and therapeutics targeted to active, latent and past-active tuberculosis need to be developed.
Diagnosis of TB, in places having the appropriate laboratory facilities, is primarily done by staining for the presence of acid-fast bacteria in respiratory sputum and by culturing of the specimen. Unfortunately, the sensitivity of a sputum smear is only about 50% and culturing of clinical specimens for the bacteria can routinely take 3 to 8 weeks.
In 1998, the complete genome sequence of Mycobacterium tuberculosis was published. Based on the published sequence, it was predicted that approximately 4000 open reading frames were present, and it was hoped that this information would lead to new vaccines and immunologic diagnosis methods. However, this sequence information cannot be used to predict whether the DNA is translated and expressed as proteins in vivo. More importantly, it is not possible on the basis of the sequences to predict whether a given sequence will encode an immunogenic or an inactive protein. In other words, the only way to determine if a protein is recognized by the immune system during or after an infection with Mycobacterium tuberculosis is to produce the given protein and test it in an appropriate assay.
Thus, there is a real need for the development of fast and effective immunologic assays to aid in the detection of TB cases, since rapid diagnosis and treatment are critical for preventing the spread of this deadly disease.